Abstract
Collagen XV is a million-dalton protein with a structural role in skeletal muscle and capillaries. As with all collagens, studies of its function are hindered by the absence of good structural data: collagens are triple-helical, non-crystallizable, multidomain proteins with extensive post-translational modification that are refractory to analysis by high-resolution structural techniques. For collagen XV, this situation is compounded by the fact that it is also a proteoglycan. In this issue of the Biochemical Journal, Myers and her colleagues use rotary shadowing electron microscopy to obtain images of purified collagen XV molecules that are sufficiently detailed to show the three-lobed structure of the N-terminus and individual glycosaminoglycan side chains. Individual molecules appear as knotted strands resembling a pretzel (a pastry snack folded in a unique figure-of-eight), which contrasts with our conventional image of collagen molecules as semi-rigid rods. Importantly, collagen XV multimerizes into cruciform structures in which simpler forms have two to four molecules per complex. Immunoelectron microscopy revealed knotted collagen XV complexes bridging collagen fibrils adjacent to basement membrane. These accomplishments are made all the more impressive by the fact that collagen XV was purified from human umbilical cord, in which the protein is represented at only (1-2)x10(-4)% of dry weight!